Zollo, M;
Ahmed, M;
Ferrucci, V;
Salpietro, V;
Asadzadeh, F;
Carotenuto, M;
Maroofian, R;
... Baple, EL; + view all
(2017)
PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.
BRAIN
, 140
(4)
pp. 940-952.
10.1093/brain/awx014.
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Abstract
PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation.
| Type: | Article |
|---|---|
| Title: | PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/brain/awx014 |
| Publisher version: | http://dx.doi.org/10.1093/brain/awx014 |
| Language: | English |
| Additional information: | The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Clinical Neurology, Neurosciences, Neurosciences & Neurology, PRUNE1, microcephaly, developmental delay, normal brain development, microtubule polymerization, tubulinopathy, PERTURB MICROTUBULE DYNAMICS, H-PRUNE, CORTICAL DEVELOPMENT, CRYSTAL-STRUCTURE, TRANSGENIC MICE, SECKEL-SYNDROME, PEHO SYNDROME, MUTATIONS, PROTEIN, CANCER |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1555367 |
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